Synthesis and Development of NSAID-H2S2 Hybrids

Abstract

Hydrogen disulfide (H2S2), a reactive sulfur species, recently gained attention as it is closely linked with H2S signaling while having distinct chemical properties. H2S2 is more efficient than H2S in inducing protein persulfidation, a process core to redox signaling. Delivering this species inside cell membrane is of therapeutic interest. Due to the inherent instability of H2S2, delivering it into the cells is challenging. So far, very few synthetic H2S2 donors have been developed using enzyme, pH, fluoride, light as stimuli. These donors release an electrophilic molecule or fluorophore as a byproduct. We had tried to deliver a pharmacologically active molecule as a byproduct along with H2S2. We have taken non steroidal anti-inflammatory drugs (NSAIDs) as pharmacologically active species that are involved in antioxidant response. The goal of this project is to develop NSAID-H2S2 hybrids that, upon activation by esterase (ES), release an NSAID and H2S2, both enhancing the cellular antioxidant response synergistically.